Undifferentiated autoinflammatory disease in adults: a prospective study in 61 patients

Undifferentiated or undefined systemic autoinflammatory disease (uSAID) encompasses a group of rare, heterogeneous diseases characterized by the features of well-defined systemic autoinflammatory diseases (SAIDs), but lacking diagnostic phenotypes or genetic confirmation. We aimed to describe the phenotypes, genotypes and treatment responses of Chinese adult patients with uSAID.

The final diagnosis of uSAID was reached in 61 patients, whose organ-specific inflammation was compared and three subgroups were identified based on phenotypic similarities to well-defined SAIDs. Phenotypes, genotypes and treatment responses were analyzed in these subgroups.

Among the 61 uSAID patients, 17 had disease-onset during childhood, and 44 had adult-onset. Compared to those without pulmonary manifestations, patients with pulmonary involvement exhibited higher frequencies of myalgia, skin lesions, cardiac involvement, gastrointestinal involvement, urinary involvement, lymphadenopathy, headache, and intellectual impairments. Twenty-four patients exhibited monogenic SAID-like phenotypes, 12 had polygenic SAID-like phenotypes, and the remaining 25 were categorized as having atypical phenotypes. Among the 53 patients followed, 25% (13/53) improved spontaneously with complete or partial recovery independent of therapy. Patients with atypical phenotypes had the highest spontaneous remission rate (10/23, 43%).

This study is the first to describe the clinical and genetic features of a cohort of Chinese adult patients with uSAID. Patients with pulmonary manifestations may be more prone to developing complex phenotypes, while those with atypical phenotypes have a high rate of spontaneous remission, indicating a favorable prognosis.